The long-term objective of this research project is to develop instrumentation and accelerated reconstruction techniques that will allow researchers to measure in vivo the heterogeneous hypoxic microenvironment of tumor models grown in mice, both xenografts and genetically engineered. To achieve these goals we will evaluate a new photoacoustic CT scanner designed to take advantage of acceleration techniques recently developed for phase contrast magnetic resonance angiography (MRA) and dynamic contrast enhanced MRA (DCE-MRA), which can significantly improve temporal resolution, without sacrificing signal to noise or spatial resolution. In Phase I we will design, construct and evaluate a new PCT scanner that will acquire a sparse set of 128 "projections" uniformly distributed over the surface of a hemisphere. Our goals are to achieve sub-second temporal resolution for dynamic studies and to acquire spectroscopic data over 16 wavelengths in as little as 1.6 seconds throughout a 20-mm-diameter imaging volume. Should we succeed, we will apply these techniques in vivo to mouse models of cancer in Phase II. PUBLIC HEALTH RELEVANCE: Scientists at pharmaceutical companies and academic institutions routinely employ preclinical imaging of small animals, especially mice, to study disease progression and monitor response to therapies. We propose to develop a novel, photoacoustic-imaging device that would allow researchers to interrogate the molecular structure of disease and assess response to therapy in a preclinical setting using near infrared radiation. This device would allow researchers to quantify hemoglobin concentration, blood flow, tissue oxygenation, and the accumulation of molecular probes in targeted tissues in small animals with excellent 3-D spatial and temporal resolution. [unreadable] [unreadable] [unreadable]